1. Field of the Invention
The present invention relates to a process for producing N-substituted maleimides. More specifically, the invention relates to (i) a process for producing N-substituted maleimides which comprises subjecting either maleic anhydride and an amine or a maleic acid monoamide, which is produced from the above two compounds, to dehydrating reaction or dehydration ring closure in an organic solvent in the presence of a catalyst and (ii) a process for purifying N-substituted maleimides which comprises washing the reaction product mixture obtained by the above process (i) or a prior art process and isolating the intended pure product from the washed mixture.
N-Substituted maleimides have a wide variety of applications as starting materials or intermediates for medicines, agricultural chemicals, dyes, macromolecular compounds, etc.
2. Description of the Prior Art
Various processes of the prior art are known for producing N-substituted maleimides. An example of the known processes comprises the dehydration ring closure of a maleic acid monoamide (a maleamic acid), which is readily producible from maleic anhydride and an amine, by heating at 180.degree. C. (L.E. Coleman et al., J. Org. Chem., 24, 135-136 (1959)). According to this process, however, the yield of the intended N-substituted maleimide is as low as 15-50%.
There is also a process, well known as a laboratory method, which comprises reacting maleic anhydride with aniline using a dehydrating agent such as acetic anhydride in the presence of a sodium acetate catalyst (Org. Synth. Coll., 5, 944 (1973)). This process, although relatively-high yields of N-substituted maleimides are obtainable thereby, has a drawback in that since the dehydrating agent needs to be used in a stoichiometric amount, the production is made expensive by the additional cost of this auxiliary material. Hence this process is unfitted for industrial production.
On the other hand, there is a process conceivable to be advantageous industrially which comprises the dehydration ring closure of a maleic acid monoamide under mild conditions wherein no dehydrating agent but an effective dehydration catalyst is used. A number of such processes are proposed, including a process employing an acidic catalyst such as sulfuric acid or sulfonic acid (British Pat. No. 1,041,027), a process employing a basic catalyst such as sodium hydroxide or triethylamine (Japanese Pat. Publication No. Sho. 47-24024, corresponding to Canadian Pat. No. 906,494 and German Pat. No. 2,100,080), and a process employing a heterogeneous catalyst such as an ion-exchange resin (Japanese Pat. Application Kokai No. Sho. 61-85359, corresponding to European Pat. No. 0,177,031 B1). According to these processes, the reaction yield (conversion to product) reaches 90% or more but the inhibition of side reaction is still insufficient; hence the reaction product mixtures contain such impurities as unreacted materials, intermediates, and various by-products and polymers, besides catalysts.
It is necessary to remove impurities sufficiently from N-substituted maleimides since these compounds are used as materials for medicines, agricultural chemicals, polymers, etc.
For the purification of N-substituted maleimides, there are proposed methods, for example, one comprising pouring the reaction product solution into a large amount of cold water, filtering the formed crystals, and further washing them with a large amount of water or organic solvent (Organic Synthesis Coll., 5, 44 (1973)); one comprising neutralizing and washing the reaction product solution with a dilute aqueous sodium carbonate solution or the like, separating the washed organic layer, and removing the solvent therefrom by distillation (Japanese Pat. Publication No. Sho. 61-204166, corresponding to U.S. Pat. No. 4,623,734); those comprising treating the reaction product solution with a strong acid such as sulfuric acid to convert by-products into resinous matter removing it, and washing the residual solution (Japanese Pat. application Kokai Nos. Sho. 61-22065 and Sho. 61-204166, corresponding to U.S. Pat. No. 4,623,734); and one comprising washing the reaction product solution with a dilute aqueous alkali solution, further washing it with water, removing the solvent by distillation, and recrystallizing the residue from an alcoholic solvent (Japanese Pat. application Kokai No. Sho. 60-10054). However, such methods as illustrated above are disadvantageous in that since the by-product formed in the step of imidization through dehydration ring closure is also insoluble in water, it is impossible to remove this by-product sufficiently by washing with water and hence a high-purity N-substituted maleimide is difficult to obtain and moreover an emulsion layer and/or a precipitate forms between the aqueous layer and the organic layer which result from the wash with water, thus worsening the separability of by-product. This is attributable to the low selectivity of the imidization through dehydration ring closure, that is, a side reaction occurring during the imidization yields a by-product having an emulsifying action or a by-product scarcely soluble in water as well as in the used organic solvent. Accordingly, when the separated organic solution containing such a by-product is subjected, as it is, to an isolation procedure such as distillation, polymerization tends to occur simultaneously and hence the yield and the purity lower. In order to avoid this, it is necessary that the organic layer and the aqueous layer, before their separation from each other, be left standing for a very long time (e.g., about two to twenty hours) and the still remaining emulsion layer be removed or that the destruction of emulsion layer and the removal of insoluble matter be forced by ultracentrifugation, filtration, or other procedure. This makes the washing step complicated and bothersome. The recrystallization from an alcohol also causes a side reaction with the alcohol or is accompanied by polymerization. Therefore it is difficult to recover a high-purity product in a high yield by this recrystallization.
On the other hand, the purification of N-substituted maleimides by distillation is also proposed (Japanese Pat. application Kokai Nos. Sho. 60-112758 and Sho. 60-112759). However, maleimides, having ethylenic double bonds, tend to polymerize upon heating in the distillation and this lowers the distillation yield. To prevent the yield drop due to such polymerization in the distillation, there are proposed methods of conducting the distillation in the presence of a stabilizer or polymerization inhibitor (Japanese Pat. application Kokai No. Sho. 61-229862, corresponding to U.S. Pat. No. 4,623,734) or conducting the distillation after neutralization of the product solution with an alkaline earth metal compound (Japanese Pat. application Kokai No. Sho. 62-138468). But the complete prevention of the polymerization cannot yet be achieved according to these methods.
As stated above, the prior techniques of purification are insufficient in the removal of impurities including by-products or in the prevention of the polymerization accompanying the distillation, hence involving problems in the yield and purity of product. Hence these techniques are still unsatisfactory for commercial production.